Antitumor Effect of Platinum-Modified STING Agonist MSA-2.

ABSTRACT

The stimulator of interferon genes (STING)-activated innate immune pathway is strong and durable for tumor immunotherapy. MSA-2 is an available non-nucleotide human STING agonist that promotes the tumor immunotherapy of STING activation. However, strategies for remolding and improving the immunotherapy effects of MSA-2 are of value for clinical applications. Here, we synthesized the platinum salt-modified MSA-2 (MSA-2-Pt) due to platinum salt being a classic chemotherapeutic drug. We found that MSA-2-Pt could achieve double-effect antitumor immunotherapy, including inducing cell death by platinum and activating the STING pathway by MSA-2. In the colon carcinoma MC38 model (sensitive to immune checkpoint immunotherapy tumor) and melanoma B16F10 model (poorly immunogenic and highly aggressive tumor), the MSA-2-Pt had a good antitumor effect, which was a little better than MSA-2 with intratumor injections. The results present a promising strategy for STING activation in tumor immunotherapy and broadening platinum-based drugs.